Natural Progesterone for the Perimenopausal Transition
by Jeffrey Dach MD

The conventional teaching is that perimenopause is a state of estrogen deficiency. That teaching is simply wrong. The first hormonal failure of the midlife transition is loss of reliable ovulation leading to loss of progesterone production. Progesterone is produced by the corpus luteum of the ovary after ovulation. So when there is no ovulation, there is no progesterone production.

Header Image: courtesy of Dr. Jerrilynn Prior, founder and scientific director of CemCor

What is happening to estrogen levels at this same time during the perimenopausal transition?  Estradiol does not decline in a smooth line. As ovarian function starts to fail, estrogen levels will fluctuate wildly due to LH stimulation. This high estrogen causes uncomfortable symptoms of estrogen dominance. Brain stimulation, Fluid retention, snappy behavior, mood disturbance, etc.

During normal menstrual cycles in younger women, high estrogen levels during luteal phase will be balanced by progesterone which opposes the effects of estrogen. However, the perimenopausal female has no progesterone!  Therefore, the solution to treatment and the obvious missing piece of the puzzle is oral micronized progesterone.

Dr. JoAnn Manson and Mainstream Medicine on Treatment of Perimenoapuse

Q&A: Is Perimenopause a Medical Condition?

In this above 2026 article on Medscape, JoAnn Manson, MD, MPH, DrPH, discusses the management of perimenopause and its ascendance in the minds of women and the media. Dr. Manson writes:

No gold standard therapy exists; options include low-dose OCPs, SSRIs/SNRIs, gabapentin, lifestyle measures.

Notice there is no mention of natural progesterone by Dr. Jo-Ann Manson who suggests treatments such as oral birth control pills, SSRI antidepressants, Gabapentin, and lifestyle measure, none of which contain natural progesterone. These are all poor choices. And, this is one of the errors of modern medicine, ignoring the valuable benefit of natural progesterone for peri-menopause. (11)

Dr. Jerrilynn Prior to the Rescue with Natural Progesterone

Professor Jerry Lynn Prior is a Professor of Endocrinology and Metabolism at the University of British Columbia in Vancouver. She founded the Centre for Menstrual Cycle and Ovulation Research (CeMCOR) in 2002 and remains its Scientific Director.

Dr. Prior recommends 300 mg of oral micronized progesterone nightly for the perimenopausal woman having symptoms of insomnia, night sweats and hot flashes. (9)

The Endocrine Pattern of Perimenopause

In 2011, Dr. Jerry-Lynn Prior describes the perimenopausal transition as a state of estrogen excess with lack of progesterone. At the same time estradiol levels fluctuate erratically. Ovulation becomes infrequent or absent. Progesterone production becomes insufficient. The most symptomatic women have higher estradiol and lower progesterone.

In 2011, Dr. Jerry Lynn Prior proposed oral micronized progesterone, 300 mg at bedtime, as a physiology-based treatment for the woman who seeks care.(1) (9)

In menstruating midlife women, cyclic use on days 14–27, or 14 days on and 14 days off, may reduce cyclic vasomotor symptoms, improve sleep, and lessen premenstrual breast pain. Heavy menstrual bleeding may be treated with ibuprofen together with progesterone on cycle days 4–28. In late perimenopause, daily bedtime progesterone is used for night sweats and insomnia.

Dr Prior argues against treating high, erratic estradiol with still more estrogen, oral contraceptives, or hysterectomy as first measures. The correct treatment is oral micronized progesterone. Dr. Prior’s studies used 300 mg oral progesterone nightly. (1)

The Clinical Trial Record

In 2012, Drs. Christine L Hitchcock and Jerrilynn C Prior conducted a randomized, placebo-controlled trial of oral micronized progesterone 300 mg at bedtime in healthy women early after menopause. (2)

Vasomotor symptom scores declined more with progesterone than with placebo. Oral micronized progesterone was effective for hot flushes and night sweats in that population. (2)

Review of the Literature 2018

In 2018, Dr. Jerrilynn Prior reviewed the medical literature on using progesterone for perimenopause, and concluded that oral micronized progesterone improves vasomotor symptoms and sleep. Reviewing the avilable studies, Dr Prior found no cardiovascular safety concerns. Dr Prior also found progesterone is breast cancer preventive, and does not increase risk for breast-cancer signal associated with synthetic progestins such as medroxyprogesterone and norethisterone. (3)

Safety of progesterone as breast cancer preventive was demonstrated in 2008 by Dr. Agnes Founier in the French Cohort study. This was an 8-year prospective cohort study (E3N) in more than 80 000 menopausal women showed progesterone prevented breast cancer in estrogen-treated women.(8)

Randomized Trial 2023

In 2023, Dr. Jerrilyn Prior published a perimenopausal clinical trial using progesterone in perimenopausal women. This was a double-blind, randomized study of 189 Canadian women, ages 35–58, who had menstruated within the previous year. The dose was 300 mg oral micronized progesterone at bedtime for three months. Women assigned to progesterone reported fewer night sweats, improved sleep quality, and less perimenopause-related life interference. No serious adverse events were reported.

The conclusion from these studies is straightforward. Progesterone has benefit in perimenopause. Sleep benefit is the most consistent finding. Night sweats improve in secondary analyses.

As mentioned above, Dr. JoAnn Manson and mainsteram medicine has not accepted progesterone as first-line treatment for perimenopausal symtoms. However, it should be. Progesterone is a rational, yet underused option. (4) (11)

Why Mainstream Guidelines Still Begin with Estrogen

The North American Menopause Society (2022) position statement says that estrogen hormone therapy remains the most effective treatment for bothersome vasomotor symptoms and for prevention of bone loss [5].

For healthy women younger than 60 years, or within ten years of menopause onset, the benefit-risk ratio is favorable in the absence of contraindications. When prescribing estrogen, a progestogen is required with systemic estrogen in the woman with a uterus. The purpose of that progestogen is endometrial protection. The position statement does not adopt progesterone monotherapy as standard first treatment for perimenopause.  (5)

Shyam (2024), reporting comments by Dr. JoAnn Manson, restates the post-WHI consensus: estrogen hormone therapy should not be withheld from appropriately selected women in early menopause [6].

Dr. Manson has also noted that newer regimens, including transdermal estradiol and micronized progesterone, require larger randomized trials.

Again, this is an error. Natural progesterone should be first line treatment, not estrogen. Perimenopausal women are symptomatic because they have high estrogen and no progesterone.

Breast Cancer Risk and Natural Progesterone Vs. Synthetic Progestins

In 2008, Dr Agnes Fournier studied the French E3N cohort, finding that breast-cancer risk varied by the type of hormone formulation. The use of natural progesterone carried no increased risk. However the use of synthetic progestins (progestogens) combined with estrogen carried increased breast cancer risk. (7)

Estrogen (estradiol) plus progesterone is not associated with increased risk in E3N French Cohort study analysis. However, estrogen plus other progestagens such as medroxyprogestrerone and noresthisterone DO increase risk for breast cancer. This is observational evidence which I accept, and is a sufficient reason to prefer micronized progesterone over medroxyprogesterone acetate when a progestogen is indicated for prevention of endometrial hyperplasia. (7)

Different Types of Natural Progesterone

The generic Prometrium version of oral progesterone is an FDA approved pharmaceutical preparation of natural progesterone available at the corner drug store (Solvay 1998). Prometium was granted FDA approval for prevention of endometrial hyperplasia. (10)

In my opinion, the compounded oral micronized progersterone is preferable to generic prometrium which contains peanut oil. The compounded oral progesterone capsule is preferable because it does not contain peanut oil, dyes, gelatin, and the dosage is adjustable and not fixed at 100/200 mg per capsule.

In 2024, Dr. Jerrilynn Prior states that topical progesterone cream lacks adequate evidence for treatment of symptomatic perimenopause or menopause. Cream products are commercially convenient, however, Dr Prior does not consider topical progesterone cream a substitute for oral micronized progesterone which has been studied and shown to prevent endometrial hyperplasia. (8)

Clinical Use in the Perimenopausal Woman

In 2011 and 2023 Dr. Jerrilynn Prior says progesterone is most applicable to the woman who still have menstrual flow and whose symptoms suggest progesterone deficiency with high or fluctuating estradiol: insomnia, premenstrual mastalgia, cyclic or nocturnal sweats, and menorrhagia [1, 4].

In that setting, bedtime oral micronized progesterone is a logical first hormone choice. When contraception is needed, mainstream medicine offers oral contraceptive pills. They are not, however, a physiologic replacement for the missing luteal hormone, progesterone.

Dr. Prior is Correct.

What is missing from much of current mainstream practice is the routine consideration of natural progesterone for perimenopause transition. This is the early phase when ovulation first starts to fail.

For women considering use of natural progesterone for perimenopausal sypmtoms, it is suggested you seek the guidance of a knowledageble physician who has experience prescribing natural progestrerone and can assist you with progesterone dosage, route of administration, cyclic versus continuous use, evaluation of abnormal bleeding, thrombotic risk, mood effects, and the possible need for estrogen or contraception require individual clinical judgment.

Dr. Phyllis Bronson’s Use of Progesterone for Perimenopause

No discussion of progesterone is complete without acknowledging the contributions made to the field by Dr. Phyllis Bronson, author of the book, Moods, Emotions, and Aging: Hormones and the Mind-Body Connection (left image book cover courtesy of Phyllis Bronson) 

1. Book chapter
Bronson, Phyllis J. “Moods, Emotions, and Aging: Hormones and the Mind-Body Connection, Rowman and Littlefield, 2013, pp. 23–38. https://doi.org/10.5040/9798216401889.ch-2
Library record: https://archive.org/details/moodsemotionsagi0000bron

Dr. Bronson argues that natural progesterone has been overlooked because of the focus on estrogen. Dr. Bronson separates progesterone, the ovarian steroid, from progestins, the synthetic hormone class used in birth-control pills to sustain the endometrium and block ovulation. She cites Katharina Dalton and John Lee for the view that unopposed estrogen produces fibrocystic breasts, fibroids, and higher endometrial and breast-cancer risk.

Applied to perimenopause, the chapter’s logic is that the first failure is often luteal: while menstrual cycles continue, estradiol still rises and falls, but progesterone is missing after anovulatory cycles. She treats that missing progesterone signal as the reason midlife mood symptoms appear.

Left image courtesy of Phyllis Bronson, Ph.D Biochemical Consulting Company Biochemical Research Foundation Aspen, Colorado. Phyllis Bronson, Ph.D., holds a doctorate in biochemistry, and is an Adjunct Associate Professor at The University of Denver.

2. Dr. Bronson discusses perimenopause in this paper: Bronson, Phyllis J. “The Effect of Neurosteroids on Depression in Peri-menopausal Women.” Journal of Orthomolecular Medicine, vol. 20, no. 3, 2005, pp. 210 ff. https://www.orthomolecular.org/library/jom/2005/pdf/2005-v20n03-p210.pdf

This is Dr. Bronson’s only detailed published account of the perimeopausal transition. In an observational study, 12 women in late perimenopause were followed for four years, and serum hormones studied. The women were categorized using Dr Bronson’s own mood scale questionairre into either anxiety-prone or depression-prone women. Serum hormones were tracked. The women classified as anxious had very high estradiol over 150 pg/mL with low progesterone under 3.3 ng/mL.

One perimenopausal woman had extremely high estradiol of 641.8 pg/mL and progesterone of only 5.1 ng/mL at the start. Her severe anxiety was treated with transdermal progesterone 100 mg/g up to six times a day. After which estradiol dropped toward 150 pg/mL with new onset of headaches, lethargy, and flat mood. The low estrogen was treated with 1 mg/g transdermal estradiol, with good results.

Across the group Dr. Bronson used transdermal progesterone from 100 mg to 800 mg twice daily. Other women started near 150 pg/mL estradiol and later fell below 50 pg/mL, which she thought vasoconstrictive headaches.

Dr. Bronson’s perimenopause model has two-stages. Firstly, ovulation fails, progesterone is low or absent, and estradiol continues to spike with dramatic fluctuations; she calls this the anxiety pattern and attributes calming effects to progesterone metabolite, allopregnanolone, acting at GABA-A receptors.

Second, estradiol itself falls by about 25 percent over four to eight months, even in women who began with “estrogen dominance.” She says luteal estradiol below 150 pg/mL, and especially a fall from an optimal 200–300 pg/mL to 120–130 pg/mL on day 20, worsens PMS if progesterone is still present, because progesterone receptors are made only when estrogen is adequate. Depression, fatigue, low libido, low motivation, vaginal dryness, and collagen loss are estrogen-deficiency symptoms, not progesterone-deficiency symptoms.

3. Bronson, Phyllis. “In Defense of Estrogen.” Riordan Clinic, 2 Dec. 2016. https://riordanclinic.org/2016/12/in-defense-of-estrogen/

This later essay shifts the emphasis from progesterone to estrogen. Estradiol is “the critical molecule” for the aging woman; progesterone is important but secondary. Dr. Bronson says mood changes track hormonal fluctuation across life, and that in the midlife transition falling estradiol levels raise monoamine-oxidase activity, lowering “feel good hermones” serotonin, norepinephrine, and dopamine. Rising estradiol after menses (after day 5) is when many women with flat affect will feel better. Excess progesterone without enough estradiol, she warns, can deepen depression in vulnerable women. Synthetic progestins, especially medroxyprogesterone acetate, cause emotional side effects, fluid retention, and the harms, as seen with the combination of  medroxyprogesterone with conjugated equine estrogens in the Women’s Health Initiative Memory Study. Progestin containing birth-control pills are called the wrong midlife choice, with natural progesterone as the correct choice.

For the perimenopause pattern of low or absent progesterone and wild estradiol swings, the essay does not recommend progesterone alone. It says the swings matter, but the lasting mood problem is the downward trend in estradiol, and that transdermal estradiol can lift mood within hours in her clinical observation.

4. “Missing the Mark on Progesterone”, Bronson, Phyllis, and Carol Petersen. YouTube, uploaded by Jill Chmielewski, 20 Sept. 2025. https://www.youtube.com/watch?v=lecsWcdlFcg

In this interview Dr. Bronson says she has studied progesterone and mood for 27 years. She treats oral progesterone as useful for severe insomnia, and transdermal progesterone through the day for anxiety, including women trying to taper off and stop benzodiazepines and Z-sleeping pills. She says women with a long progesterone deficit should not be started on very low doses of progesterone; one starting regimen she describes is 100 mg oral progesterone four times a day. For cycling women she allows cyclic, luteal phase use, but says anxious women often need to start a week earlier. She distinguishes progesterone from progestins and argues that compounded progesterone has long been available for depression.

Dr. Bronson’s discussion of perimenopause is this: “progesterone is missing while menstrual cycles continue”. There is erratic ovulation, low luteal progesterone, worsening anxiety and insomnia. This should be treated with enough bioidentical progesterone rather than an SSRI or a progestin.

5. “Defending all Forms of Bioidentical Progesterone”
Bronson, Phyllis, and Carol Petersen. YouTube, 3 Aug. 2025. https://www.youtube.com/watch?v=mMx9SlwILcE

Dr. Bronson rejects Suzanne Somers-style cycling for older women as biochemically pointless, because it withholds progesterone on the days when women need it, when their mood is unstable. Cycling women may need it only half the month; women with anxiety may need it earlier; women who “desperately need” progesterone, need it every day. She calls progesterone the mood balancer, says it works with estradiol rather than as a brake against it, and says the practical reason for enough progesterone is to keep the endometrium from thickening to pervent endometrial hyperplasia. She also reminds us: if estradiol is low and progesterone is high, calm may be followed by a return of depression.

Dr Bronson’s suggestion for menopausal transition or perimenopause: For early perimenopause, with intermittent ovulation, one might try cyclic luteal phase progesterone. For late perimenopause, with long anovulatory stretches and wild estradiol spikes, this is where daily progesterone is needed. Estradiol may also be added in selected cases.

6. “Progesterone Q & A” Bronson, Phyllis, and Carol Petersen. YouTube, uploaded by Jill Chmielewski, 23 Oct. 2025. https://www.youtube.com/watch?v=V6sXgKrbxBs

Dr. Bronson discusses her book, Moods, Emotions, and Aging and says her work is the biochemical connection of hormones to mood. Hormones, in her phrase, are “containers for mood” : balanced hormones let a woman contain emotional swings. The recorded discussion also covers progesterone versus progestins. Dr Bronson notes that transdermal progesterone is absorbed even when serum levels do not rise. She discusses that progesterone may produce grogginess, and high progesterone may downregulate estrogen receptors.

For perimenopause, Dr. Bronson’s point is this is when progesterone is absent and estradiol is swinging, this causes an associated mood disorder. Replacing progesterone restores mood, provided estradiol is not allowed to fall too far.

7. “Debunking the Continuous Progesterone Myth”
Bronson, Phyllis, et al. The Tara Thorne Wellness Podcast, episode 171, 10 Sept. 2026. https://sites.libsyn.com/425186/website/171-debunking-the-continuous-progesterone-myth-unopposed-estradiol-is-the-real-concern-with-phyllis-bronson-phd-jill-chmielewski-rn-bsn-carol-petersen-rph-cnp

Unopposed estradiol is the main concern during perimenopause with fluctuating or high estradiol without progesterone. This is the problem, and daily progesterone is a response to absent luteal progesterone.

Articles with related Interest:

Moods, Emotions, and Aging by Phyllis Bronson PhD (book review)

Progesterone for Prevention of Endometrial Hyperplasia

Jeffrey Dach MD
7450 Griffin Road Suite 180/190
Davie, Fl 33314
954-792-4663

References

1. Prior, Jerilynn C. “Progesterone for Symptomatic Perimenopause Treatment – Progesterone Politics, Physiology and Potential for Perimenopause.” Facts, Views & Vision in ObGyn, vol. 3, no. 2, 2011, pp. 109-120.

2. Hitchcock, Christine L., and Jerilynn C. Prior. “Oral Micronized Progesterone for Vasomotor Symptoms—A Placebo-Controlled Randomized Trial in Healthy Postmenopausal Women.” *Menopause*, vol. 19, no. 8, 2012, pp. 886-893.

3. Prior, Jerilynn C. “Progesterone for Treatment of Symptomatic Menopausal Women.” Climacteric, vol. 21, no. 4, 2018, pp. 358-365.

4. Prior, Jerilynn C., et al. “Oral Micronized Progesterone for Perimenopausal Night Sweats and Hot Flushes: A Phase III Canada-Wide Randomized Placebo-Controlled 4 Month Trial.” *Scientific Reports*, vol. 13, no. 9082, 2023.

https://www.nature.com/articles/s41598-023-35826-w

5. The North American Menopause Society. “The 2022 Hormone Therapy Position Statement of The North American Menopause Society.” *Menopause*, vol. 29, no. 7, 2022, pp. 767-794.

https://pubmed.ncbi.nlm.nih.gov/35797481/

6. Shyam, Anila. “Understanding Hormone Therapy: Insights from Dr. JoAnn Manson.” *MenoChannel*, 24 May 2024. https://www.menochannel.com/blog/dr-joann-manson

7. Fournier, Agnès, Franco Berrino, and Françoise Clavel-Chapelon. “Unequal Risks for Breast Cancer Associated with Different Hormone Replacement Therapies: Results from the E3N Cohort Study.” *Breast Cancer Research and Treatment*, vol. 107, no. 1, 2008, pp. 103-111.

8. Prior, Jerilynn C. “Progesterone – Q&A with Prof. Jerilynn Prior.” *MenoClarity*, 11 June 2024.

Progesterone – Q&A With Prof. Jerilynn Prior

9. Prior, Jerilynn C., et al. “Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial.” Scientific reports 13.1 (2023): 9082.

10. (Schering Corporation; marketed/promoted by Solvay Pharmaceuticals) for FDA approval of Prometrium (micronized progesterone) for prevention of endometrial hyperplasia.

The supporting data came from a proprietary randomized, double-blind clinical trial submitted as part of NDA 020843 (approved 26 December 1998). Results are summarized in the FDA product labeling and NDA review documents rather than a standalone published paper.

11. Q&A: Is Perimenopause a Medical Condition?  Medscape (Dr. JoAnn MAnson)  by Whitney McKnight, September 11, 2026

Article Key Points

Perimenopause = clinical dx; irregular menses near age ≥45 most suggestive.
Hormone levels fluctuate widely; blood tests for perimenopause are not reliable clinically.
Intermittent ovulation persists; unplanned pregnancy risk remains, so contraception still needed.
Midlife symptoms may reflect thyroid disease or autoimmune disorders, not perimenopause alone.
No gold standard therapy; options include low-dose OCPs, SSRIs/SNRIs, gabapentin, lifestyle measures.